Search Results (7)

The aim of this study was to investigate the potential for co-bioleaching of ground printed circuit boards (PCBs) and flotation tailings using a single-stage biohydrometallurgical process. The ground PCB sample was a finely divided waste product from industrial shredding, which was collected using an air filtration system. The flotation tailings sample was mainly composed of pyrite (49%), quartz (29%), gypsum (8%), feldspar (8%), and chlorite (6%). The experiment was carried out in laboratory-scale reactors at 35 °C with constant aeration and a flotation tailings pulp density of 5% (solid-to-liquid ratio). In a control reactor, only flotation tailings were leached. In an experimental reactor, both flotation tailings and ground PCBs were leached simultaneously. The experiment was conducted in two stages. In the first stage, the experiment was carried out in a batch mode. The second stage involved two reactors operating continuously in cascade. During the experiment, we monitored the dynamics of several key parameters as a function of PCB concentration, including pH, redox potential, the concentrations of Fe³⁺ and Fe²⁺ ions, and the number of microbial cells. The 16S rRNA gene analysis revealed that the presence of PCBs had a significant effect on the composition of the microbial community. The concentration of PCB was gradually increased in order to examine the limits of the process and optimize potential economic benefits. The increase was done in 3 stages: 5 g/L in the first stage, from 5 to 12 g/L in the second stage, and up to 35.5 g/L in the third stage. However, this increase had a negative effect on the pyrite oxidation rate and the effectiveness of PCB bioleaching in continuous mode. The bioleaching efficiency of copper from printed circuit boards (PCBs) was above 70% in batch mode and above 80% in continuous mode at PCB concentrations up to 12 g per liter. Copper recovery decreased to around 53.1–61.6% as the PCB concentration continued to increase. The nickel leaching efficiency in batch mode was 46.3 ± 4.8%. In continuous mode, the nickel recovery decreased as the PCB concentration increased, reaching 48.53% in the first stage, then declining to 37.62% in the second stage and finally dropping to 27.06% in the third stage, depending on the higher concentration of PCB. Full article

The heart–brain axis is a bidirectional communication network composed of neural, humoral, and immune pathways that sustain cardiovascular and brain homeostasis. There is mounting evidence that viral myocarditis—a prototype of inflammatory heart disease—acts beyond the myocardium, triggering systemic immune cascades that lead to central nervous system (CNS) involvement. This involvement creates an inflammatory continuum in which cardiac damage and neuroinflammation reinforce each other via common cytokine and molecular mediators. Central mediators in this axis are the proinflammatory cytokines IL-1β, IL-6, tumor necrosis factor (TNF)-α, IL-17, IL-23, and IL-33. These cytokines are released by infected cardiomyocytes and immune cells during myocarditis, inducing endothelial cell (EC) activation, and causing blood–brain barrier (BBB) disruption. Simultaneously, TLR/NF-κB signaling and the stability of endothelial junctions are modulated by regulatory microRNAs such as miR-155 and miR-146a/b, which respectively enhance or attenuate inflammatory signals. Disruption of the BBB allows cytokines and immune cells to enter the brain parenchyma, where they activate microglia and astrocytes through NF-κB-dependent pathways. The resultant neuroinflammation disrupts autonomic equilibrium and leads to sympathetic overdrive, arrhythmogenesis, and overall worsening of cardiac injury, thus forming a self-perpetuating inflammatory cycle between the heart and the brain. Selective modulation of cytokines (anti-IL-1β, IL-6 receptor antagonists, and TNF-α modulators), blockade of the NLRP3 inflammasome, and miRNA therapy (anti-miR-155 and miR-146a mimics) are potential approaches for interrupting the heart–brain inflammatory circuit. In addition, neurotrophic therapies preserving BBB integrity may reduce secondary neuronal damage. Therefore, a future precision cardio-neuroprotective paradigm will rely on the integration of anti-inflammatory, molecular, and neurovascular strategies aimed at limiting systemic cytokine propagation and restoring bidirectional homeostasis through the heart–brain axis. Full article

Colorectal cancer (CRC) is a significant cause of cancer mortality in the world, and its etiology is complicated by genetic and epigenetic changes. As one of the most important tumor progression regulators, Zinc Finger E-box Binding Homeobox 1 (ZEB1) is a transcription factor that has a key role in epithelial–mesenchymal transition (EMT), which is essential in the metastasis, drug resistance, and plasticity of cancer cells in CRC. ZEB1 silences the expression of epithelial markers, including E-cadherin, and it induces the development of mesenchymal properties, such as invasion and metastasis, i.e., tumor aggressiveness. ZEB1 drives epigenetic reprogramming in CRC by coordinating histone deacetylation, histone methylation, and DNA methylation of epithelial tumor suppressor gene promoters and by engaging in reciprocal regulatory interactions with non-coding RNAs, including the miR-200 family. Furthermore, multiple oncogenic signaling cascades, including Wnt/β-catenin, TGF-β, NF-κB, MEK-ERK, JAK/STAT3, and HIF-1α, converge on ZEB1 to amplify its transcriptional and epigenetic activity, positioning ZEB1 as a nodal integrator of extracellular cues and epigenetic reprogramming in CRC metastasis. This review integrates three interconnected regulatory layers, i.e., (1) ZEB1’s direct epigenetic control of target gene expression via histone modification and DNA methylation, (2) post-transcriptional regulation of ZEB1 itself by ncRNAs (miRNAs, circRNAs, and lncRNAs) that create feedback circuits modulating layer 1, and (3) upstream modulation of ZEB1 transcriptional activity by oncogenic signaling pathways (Wnt/β-catenin, TGF-β, NF-κB, MEK-ERK, JAK/STAT3, and HIF-1α) to provide a comprehensive picture of ZEB1 in CRC metastasis and its therapeutic implications. Full article

Ligand-activated Retinoid X Receptors (RXRs) regulate gene networks essential for neural development, neuroinflammation, and metabolism. Understanding how RXR activation influences chromatin architecture and gene expression may reveal mechanisms relevant to neurodegenerative diseases. We used Bexarotene-treated APP/PS1ΔE9 mice to study RXR-mediated regulatory mechanisms by integrating single-nucleus ATAC-seq (snATAC-seq) with single-cell RNA-seq (scRNA-seq) and validating differentially accessible chromatin peaks using RXR ChIP-seq. Transcription factor (TF) footprinting analysis mapped regulatory networks activated by ligand-bound RXR. Our integrated analyses revealed a multilayered transcriptional cascade initiated by RXR signaling. We identified RXR-centered regulatory circuits involving heterodimer activation, upregulation of downstream TFs, and induction of metabolic pathways relevant to neural function. Detailed analysis of neuronal TF networks revealed that Bexarotene modulates RXR’s role through existing regulatory scaffolds rather than creating new ones. This study demonstrates that combining scRNA-seq, snATAC-seq, and ChIP-seq enables comprehensive analysis of RXR-mediated transcriptional regulation. RXR activation orchestrates cell-type-specific chromatin remodeling of gene networks controlling neuroinflammation, lipid metabolism, and synaptic signaling, providing mechanistic insights into RXR-dependent transcriptional programs in Alzheimer’s disease pathology. Full article

MicroRNA-483 regulates multiple human disease categories, spanning oncology, cardiopulmonary, metabolic, immune, neurological, and musculoskeletal pathologies. We integrate experimentally validated interactions from 146 studies to construct a comprehensive regulatory network, encompassing transcription factors, long non-coding RNAs, circular RNAs, and messenger RNA targets. Our analysis reveals that miR-483 promotes tumorigenesis by suppressing tumor-suppressive checkpoints, yet it protects cardiopulmonary, metabolic, and neurological tissues from pathological injury. This functional duality arises from tissue-specific modulation of shared signaling pathways, particularly TGF-β and MAPK cascades, which function as the core hubs driving its context-dependent activity across six disease categories. By mapping miR-483 regulatory circuits across multiple diseases, we define the molecular determinants of its context-dependent activity. These findings establish miR-483 as both a diagnostic biomarker and a therapeutic target whose function is dictated by cellular context. Full article

This study developed an artificial chimeric intron module with an RNA riboswitch and TetR aptamer that were integrated into essential gene exons. Doxycycline can modulate Pre-mRNA alternative splicing, modify the exon reading frame, and dynamically regulate gene expression. By shifting the aptamer 2 base pair within the switch, we unexpectedly obtained the “on-switch” CTM and “off-switch” C2ITetR>4A, which possess thoroughly contrasting regulatory functions. The CTM module can conditionally induce tumor cell apoptosis and regulate genes reversibly and sustainably following doxycycline induction. We integrated the C2ITetR>4A/CTM switches with the L7Ae/k-turn module to create an intron-spliced double-switched RNA cascade system. The system can both activate and inhibit the splicing mechanism utilizing the same ligand to minimize crosstalk among aptamer switching elements, control target gene leakage, and enhance the dynamic range of gene expression. We analyzed numerous factors affecting Pre-mRNA splicing to identify the optimal equilibrium point for switch regulation. This will enable precise predictions of dynamic regulatory efficiency and the rational design of genetic modules, thereby providing a valuable instrument for mammalian synthetic biology. Full article

DNA methylation, a modification found in most species, regulates chromatin functions in conjunction with other epigenome modifications, such as histone post-translational modifications and non-coding RNAs. In mammals, DNA methylation has essential roles in development by orchestrating the generation and maintenance of the phenotypic diversity of human cell types. This Special Issue of Genes contains eight review articles, which cover several aspects of epigenome regulation by DNA methyltransferases (DNMTs), the enzymes responsible for the introduction of DNA methylation. The manuscripts present the most recent advances regarding the structure and function of DNMTs, their targeting and regulation by interacting factors and chromatin modifications, and the roles of DNMTs in mammalian development and human diseases. However, many aspects of these important enzymes are still insufficiently understood. Potential directions of future work are the regulation of DNMTs by post-translational modifications and their connection to cellular signaling and second messenger cascades on one hand and to large multifactorial epigenetic chromatin circuits on the other. Additionally, technical advancements, including the availability of designer nucleosomes and the rapid development of cryo-electron microscopy are expected to trigger breakthrough discoveries in this exciting field. Full article